p97抑制剂EerⅠ诱导胃癌细胞系AGS的凋亡与铁死亡

doi:10.16352/j.issn.1001-6325.2025.11.1401

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (11): 1401-1408.doi: 10.16352/j.issn.1001-6325.2025.11.1401

p97抑制剂EerⅠ诱导胃癌细胞系AGS的凋亡与铁死亡

李文华¹, 王润霖¹, 康乾鹏², 黄梅², 郭正光^1*, 张春林^2*, 黄永胜^1,2*

1.中国医学科学院基础医学研究所北京协和医学院基础学院,北京 100005;
2.贵州医科大学基础医学院分子生物学重点实验室, 贵州贵阳 561113

收稿日期:2025-06-13 修回日期:2025-07-17 出版日期:2025-11-05 发布日期:2025-10-24
通讯作者: ^*yongshengH83@126.com; 362326474@qq.com; gzg0625@sina.com
基金资助:
北京市自然科学基金(7232105);国家重点研发计划(2016YFC1302203)

p97 inhibitor EerⅠ induces apoptosis and ferroptosis of gastric cancer cell line AGS

LI Wenhua¹, WANG Runlin¹, KANG Qianpeng², HUANG Mei², GUO Zhengguang^1*, ZHANG Chunlin^2*, HUANG Yongsheng^1,2*

1. Institute of Basic Medical Sciences CAMS, School of Basical Medicine PUMC, Beijing 100005;
2. Key Laboratory of Molecular Biology, School of Basic Medicine, Guizhou Medical University, Guiyang 561113, China

Received:2025-06-13 Revised:2025-07-17 Online:2025-11-05 Published:2025-10-24
Contact: ^*yongshengH83@126.com; 362326474@qq.com; gzg0625@sina.com

摘要/Abstract

摘要： 目的探究p97抑制剂EerⅠ诱导胃癌细胞系AGS死亡相关的分子机制。方法通过EerⅠ 处理AGS细胞,采用高效液相色谱质谱联用技术进行蛋白质组分析,筛选差异表达蛋白质并寻找关键信号通路。同时,利用蛋白质免疫印迹验证了相关信号通路的蛋白质表达; 利用 CCK-8试剂盒检测了细胞增殖;利用TUNEL染色试剂盒检测了细胞凋亡;利用Liperfluo探针检测铁死亡途径相关脂质过氧化物。结果相比对照组,EerⅠ处理组中257个蛋白质发生显著变化 (fold change＞1.5 和P＜0.05), 其中125个蛋白升高, 132个蛋白质降低,这些差异表达蛋白质(DEPs) 经富集分析后表明EerⅠ可能显著影响细胞凋亡、铁死亡等细胞死亡相关的信号通路。并且, EerⅠ可以增加细胞凋亡相关的基因组DNA断裂,增加铁死亡途径的脂质过氧化物,引起细胞死亡相关的蛋白质变化,并显著抑制胃癌细胞的增殖。结论 p97抑制剂EerⅠ能通过细胞凋亡和铁死亡途径诱导胃癌细胞系AGS死亡,从而抑制肿瘤细胞增殖。

关键词: 胃癌, p97蛋白, 铁死亡, 细胞凋亡

Abstract: Objective To investigate the molecular mechanism of the induction of gastric cancer cell line AGS death by p97 inhibitor eeyarestatinⅠ (EerⅠ). Methods AGS cells were treated with EerⅠ. Then liquid chromatography-mass spectrometry was used to perform proteome analysis for screening differentially expressed proteins and to find underlying signaling pathways. At the same time, the proteins of related pathway were investigated by protein immunoblotting. Cell proliferation was detected using the CCK-8 test kit; Cell apoptosis was detected using TUNEL staining test kit; Liperfluo probe was used to detect ferroptosis-related lipid peroxides. Results In EerⅠ treatment group, there were significant changes in proteins(fold change＞1.5 and P＜0.05), in which 125 proteins were increased and 132 proteins were decreased. The enrichment analysis of these DEPs showed that EerⅠ might significantly affect cell apoptosis and ferroptosis-related signaling pathways. Furthermore, EerⅠ could increase genomic DNA fragmentation related to cell apoptosis, increase of lipid peroxides in the ferroptosis pathway, causes changes in cell death related proteins, and inhibit the proliferation of gastric cancer cells. Conclusions p97 inhibitor EerⅠ can induce cell apoptosis and ferroptosis in AGS cells, thereby inhibiting tumor cell proliferation.

Key words: gastric cancer, p97 protein, cell apoptosis, ferroptosis

中图分类号:

R730.2

李文华, 王润霖, 康乾鹏, 黄梅, 郭正光, 张春林, 黄永胜. p97抑制剂EerⅠ诱导胃癌细胞系AGS的凋亡与铁死亡[J]. 基础医学与临床, 2025, 45(11): 1401-1408.

LI Wenhua, WANG Runlin, KANG Qianpeng, HUANG Mei, GUO Zhengguang, ZHANG Chunlin, HUANG Yongsheng. p97 inhibitor EerⅠ induces apoptosis and ferroptosis of gastric cancer cell line AGS[J]. Basic & Clinical Medicine, 2025, 45(11): 1401-1408.

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p97抑制剂EerⅠ诱导胃癌细胞系AGS的凋亡与铁死亡

p97 inhibitor EerⅠ induces apoptosis and ferroptosis of gastric cancer cell line AGS

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